Type 1 diabetes (T1D) is an autoimmune disease observed in many mammalian species, governed by multiple genetic and environmental risk factors. Overt diabetes reflects glucose intolerance due to insulin deficiency. It is the end result of prediabetes, with progressive lymphoid infiltration around and then inside pancreatic islets of Langerhans, and subsequent destruction of insulin-producing β-cells by autoreactive T lymphocytes (Anderson and Bluestone, 2005). T1D is characterized by a permissive immune system that fails to impose tolerance to arrays of self-antigens. Although the initiating events are not fully understood, β-cell stress and β-cell death in the course of early islet restructuring are thought to provide sensitizing autoantigens which expand autoreactive T cell pools in pancreatic lymph nodes (Mathis et al., 2001; Rosmalen et al., 2002; Trudeau et al., 2000; Zhang et al., 2002).
Self-antigens targeted in T1D are expressed in β-cells and, in most cases, elsewhere in the body. They prominently include neuronal antigens, recognized by T cells with pathogenic potential (Salomon et al., 2001; Winer et al., 2001). It is unclear why, in T1D, T cells infiltrate only islets and their associated glia (Winer et al., 2003). It is also unclear whether autoimmunity and islet inflammation are related to hyperinsulinism and insulin resistance typical for even young NOD mice (Amrani et al., 1998; Chaparro et al., 2006).
There is evidence for functional interactions between nervous and immune systems (e.g. (Wang et al., 2003)), but connections between islet autoimmunity and the nervous system remain ill defined (Carrillo et al., 2005). The interface between nervous system, external and tissue environments is the primary sensory afferent neuron. Primary afferents also have efferent function through local release of mediators such as neuropeptides (e.g. substance P, sP and CGRP). There is evidence that islets may be innervated by primary sensory neurons, but their local function is uncertain (Ahren, 2000).